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1.
Fitoterapia ; 176: 105986, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38703914

RESUMO

In the present study, we have attempted a comprehensive assessment of the possible radioprotective efficacy of Pterocarpus santalinus aqueous extract (PSAE). All the studied models were gamma-irradiated with prior treatment with PSAE. First, the content of total phenols (4.061 µg/mg gallic acid equivalents), flavonoids (6.616 µg/mg quercetin equivalents), and tannins (0.008 mg/L of PSAE) were determined spectrophotometrically. Second, UHPLC-HRMS analysis was performed to identify the possible radioprotectors. Of those, santalins A & B are known for their usage as natural color in foods and alcoholic beverages identified in PSAE. Treatment was well tolerated with no side effects from PSAE. Later, it was shown that radiation-induced lethality significantly amended in PSAE-treated spleen lymphocytes as evidenced by reduced elevated levels of ROS and lipid peroxidation, restored total thiols and GSH: GSSG, inhibited DNA DSBs and cell death. Furthermore, an immunomodulation study was carried out because radiation exposure induces an inflammatory response. Our study shows that PSAE suppressed concanavalin A-induced T-cell proliferation as evidenced by CFSE dye dilution and CD69 antibody staining methods. Taken together, the current study explored the protective efficacy of PSAE from gamma radiation-inflicted injuries and hence we recommend PSAE as a potent radioprotective formulation.

2.
3 Biotech ; 14(1): 16, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38125651

RESUMO

The present study was designed to evaluate the anti-obesity and anti-hyperglycemic activity of Thymoquinone (ThyQ) isolated from Nigella sativa seeds. Male Wistar rats were randomly divided into five groups and fed either normal pellet diet or high-fat diet (HFD) for 18 weeks and water ad-libitum. Group I: normal pellet diet (NPD)-fed, Group II: high-fat diet (HFD)-fed, Group III: HFD-fed-ThyQ (20 mg)-treated, Group IV: HFD-fed-ThyQ (40 mg)-treated and Group V: HFD-fed-Orlistat (5 mg)-treated group. Intervention with ThyQ started from 12th week onwards to HFD-fed rats of group III and IV. ThyQ administration significantly (p < 0.01) mitigated body weight gain, blood glucose, insulin level, serum and liver lipids (except HDL) and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose tolerance test (OGTT), homeostasis model assessment-insulin resistance (HOMA-IR) and insulin tolerance test (ITT). Furthermore, ThyQ significantly (p < 0.01) diminished serum aspartate transaminase (AST), alanine transaminase (ALT), acetyl-CoA carboxylase (ACC), plasma leptin, resistin and visfatin levels but enhanced lipoprotein lipase (LPL) and adiponectin levels. RT-PCR analysis demonstrated down-regulated mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), CCAAT/enhancer-binding protein-α (C/EBP-α) and fatty acid synthase (FAS) but upregulation of Insulin receptor substrate-1 (IRS-1).Western blot analysis displayed phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in ThyQ-treated rats. Liver microtome sections of HFD-fed rats showed degenerated hepatocytes with high lipid stores while that of adipose tissue sections displayed large, fat-laden adipocytes, however, these histological changes were considerably attenuated in ThyQ-treated groups. Together these findings demonstrate that ThyQ can be a valuable therapeutic compound to potentially alleviate diet-induced obesity, hyperglycemia and insulin resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03847-x.

3.
J Cell Biochem ; 124(12): 1900-1918, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37992132

RESUMO

Epithelial-mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA-MB-231 and MCF-7 breast cancer cells. The apparent anticancer activity of UA on MDA-MB-231 and MCF-7 cells was evident from IC50 values of 14.98 and 15.99 µg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA-MB-231 and MCF-7 cells were treated with 20 µg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G0 /G1 phase, S phase, G2 /M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum-polarized-ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with -53.865, -48.971 and -40.617 MMGBSA (ΔGbind ) scores, respectively. The long-range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Células MCF-7 , Fibronectinas , Fatores de Transcrição , Pontos de Checagem do Ciclo Celular , Transição Epitelial-Mesenquimal , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
4.
3 Biotech ; 13(2): 41, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36643403

RESUMO

Capparis zeylanica L. is a climbing shrub distributed in Indian subcontinent and Mediterranean region. Almost all parts of the plant are used in folk medicine and traditional practices to treat several human ailments. The present study was aimed to investigate the role of C. zeylanica L. root extract in preventing cancerous cells growth and proliferation, as well as promoting apoptosis and cell cycle arrest in MDA-MB-231 and MCF-7 breast cancer cells. Methanolic extract of C. zeylanica L. (MECz) was prepared and characterized by LC-ESI-MS/MS analysis. In vitro cytotoxicity and anti-proliferative activity of MECz was evaluated by MTT assay, while cell viability, apoptosis and cell cycle progression by Muse Cell analyzer. Furthermore, the mRNA and protein expressions of EMT markers were assessed using qRT-PCR and western blotting techniques, respectively. The MECz was found to be rich in phenolic compounds including chlorogenic acid, 6-gingerol, and certain triterpenes like ursolic acid etc. The apparent anti-metastasis activity of MECz was evident from IC50 value of 19.12 and 24.22 µg/mL, respectively, on MDA-MB-231 and MCF-7 cells in MTT assay. An absolute decrease in cell viability (78.1-53.4% and 89.9-49.0%), augmented apoptosis (90.98-48.25% and 88.25-47.70%) and S phase, G2/M phase cell cycle arrest was found by MECz treatment on MDA-MB-231 and MCF-7 cells. The gene expression studies revealed that MECz could significantly (p < 0.001) regulate the expression of EMT markers such as snail, slug, zeb-1, twist-1, fibronectin, vimentin and E-cadherin at molecular level. These findings demonstrate that C. zeylanica L. root extract inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes and proteins. Thus, MECz may be suggested as a potential anti-metastasis agent in the treatment of breast cancer.

5.
3 Biotech ; 11(5): 233, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33968577

RESUMO

Pterocarpus santalinus has huge demand owing to its commercial and medicinal value. However, there are limited research studies on its therapeutic activity against obesity and obesity-induced inflammation and underlying mechanism of action. Therefore, in the present study, chloroform bioactive fraction of P. santalinus (CFP) was isolated and evaluated for its activity against adipogenesis and adipogenesis-induced inflammation in 3T3-L1 cell culture model. LC-MS/MS analysis of CFP was performed to identify the compounds present. CFP-treated 3T3-L1 cells (50, 100 and 200 µg/ml) have significantly (p < 0.01 or < 0.05) enhanced glycerol release and adiponectin level, but reduced lipid accumulation and leptin, and MTT assay demonstrated CFP was non-toxic till a dose of 300 µg/ml at 24 and 48 h. A considerable reduction in tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels was witnessed in lipopolysaccharide (LPS)-induced 3T3-L1 cells with CFP treatment in dose-dependent manner. Gene expression studies demonstrated down-regulation of mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein-1c (SREBP-1c), leptin, TNF-α and IL-6 but up-regulation of adiponectin and uncoupling protein-1 (UCP-1) and the same trend was observed in protein expression also. In conclusion, it is suggested that CFP could be beneficial to treat obesity and associated inflammation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32767950

RESUMO

BACKGROUND: Scientific research continues to develop more efficacious drugs to treat and cure cancer, the dreadful disease threatening the human race. Chemotherapy is an essential means in cancer therapy, however, plant drugs having pharmacological safety, can be used alone or as additions to current chemotherapeutic agents to enhance therapeutic efficacy and minimize chemotherapyinduced adverse effects. OBJECTIVE: A combination therapy where the synergistic effect on multiple targets is possible has gained significance because a one-drug one-target approach fails to yield the desired therapeutic effect. Therefore, a detailed description of important plant polyphenolic compounds with anticancer activity and their role in potentiating chemotherapeutic efficiency of existing anticancer drugs is provided in this review. Systematically screening combinations of active pharmaceutical ingredients for potential synergy with plant compounds may be especially valuable in cancer therapy. METHODS: We extensively have gone through reviews and research articles available in the literature. We made use of databases such as Google Scholar, Research Gate, PubMed, Science Direct, etc. The following keywords were used in our literature search: "Chemotherapy, drug development, cancer drugs, plant-derived polyphenolics, synergistic studies, combination therapy, diagnosis and genetics." CONCLUSION: Systematic research studies on screening combinations of plant phytochemicals with potential chemotherapeutic pharmaceuticals shed light on their synergistic effects, mechanisms of actions paving the way to develop more efficient anticancer therapeutics to treat and cure the cancer menace, to nullify chemotherapy-induced adverse effects and our review substantially contributes in this direction.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Plantas Medicinais , Polifenóis/administração & dosagem , Animais , Antineoplásicos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Sinergismo Farmacológico , Humanos , Neoplasias/diagnóstico , Neoplasias/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Polifenóis/isolamento & purificação , Polifenóis/metabolismo , Resultado do Tratamento
7.
Arch Physiol Biochem ; 126(5): 453-462, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30739501

RESUMO

In the current study, we evaluated the effects of Asiatic acid (AA) on lipid metabolic markers in HFD-induced obese Sprague-Dawley rat model. AA (20 mg/kg BW) was administered orally to HFD-fed rats for 42 days. Changes in body composition, glucose, insulin resistance (IR) and lipid profiles of tissues, plasma and the pattern of gene expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and its target genes fatty-acid synthase (FAS), adipocyte protein-2 (aP2) and uncoupling protein-2 (UCP-2) and pro-inflammatory factor tumor necrosis factor (TNF)-α were observed in experimental rats. Oral administration of AA exerts therapeutic effects similar to orlistat in attenuating body weight gain, glucose, IR, plasma and tissue lipids and mRNA levels of PPAR-γ, FAS, aP2 and inflammatory factor TNF-α and increasing UCP-2 expression in HFD-fed rats. Hence, these findings concluded that AA attenuate HFD-induced obesity by modulating PPAR-γ and its target genes and regulate lipid metabolism, suggesting their possible antiobesity effects.


Assuntos
Adipogenia , Biomarcadores/metabolismo , Dieta Hiperlipídica , Inflamação/tratamento farmacológico , Obesidade/complicações , Triterpenos Pentacíclicos/farmacologia , Animais , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Metabolismo dos Lipídeos , Masculino , Ratos , Ratos Sprague-Dawley
8.
Ecotoxicol Environ Saf ; 182: 109416, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31301596

RESUMO

The main objectives of this study were to purify the glutathione S-transfereses (GSTs) and assess the effect of high doses of acrylamide (ACR) on male albino Wistar rat liver, kidney, testis and bran GST activities, and expression analysis of GST. ACR (50 mg/300 ml) was ingested for 40 days (20 doses) in drinking water on alternative days, on 40 day post ingestion the control and treated tissues were collected for GST purification by affinity column and biochemical characterization of GSTs by substrate specificities, and GST expression by immuno dot blots. In the analysis of the purified GSTs, we observed that liver GSTs were resolved in to three bands known as Yc, Yb and Ya; kidney GSTs were resolved in to two bands known as Yc and Ya; testis and brain GSTs were resolved as four bands known as Yc, Yb, Yß and Yδ on 12.5% sodium dodecyl sulfate polyacrylamide gel (SDS PAGE). In the analysis of biochemical characterization, we observed a significant decrease (p < 0.05) in the specific activities of liver GST isoforms with the substrates 1-chloro 2,4-dinitrobenzene (CDNB), bromosulfophthalein (BSP), p-nitrophenyl acetate (pNPA), p-nitrobenzyl chloride (pNBC) and cumene hydroperoxide (CHP), but showed no activity with ethacrynic acid (ECA) and significant decrease (p < 0.05) in the specific activities of kidney GST isoforms with the substrates CDNB, pNPA, pNBC and CHP, but showed no activity with BSP and ECA, and a significant decrease (p < 0.05) in the specific activities of testis and brain GST isoforms with the substrates CDNB, BSP, pNPA, pNBC, ECA and CHP. In the analysis of immuno dot blots, we observed a decreased expression of liver, kidney, testis and brain GSTs. Through the affinity purification and biochemical characterization, we observed a tissue specific distribution of GSTs that is liver GSTs possess Yc, Yb and Ya sub units known as alpha (α) and mu (µ) class GSTs; kidney GSTs possess Yc and Ya sub units known as (α) alpha class GST; testis and brain GSTs possess Yc, Yb, Yß and Yδ sub units known as alpha (α), mu (µ) and pi (π) class GSTs. Purification studies, biochemical characterization and immuno dot blot analysis were revealed the GSTs were sensitive to high doses of ACR and the high level exposure to ACR cause the damage of detoxification function of GST due to decreased expression and hence lead to cellular dysfunction of vital organs.


Assuntos
Acrilamida/toxicidade , Glutationa Transferase/metabolismo , Animais , Eletroforese em Gel de Poliacrilamida , Glutationa/metabolismo , Isoenzimas , Rim/metabolismo , Fígado/metabolismo , Masculino , Nitrobenzenos , Nitrofenóis , Ratos , Ratos Wistar , Especificidade por Substrato , Testículo/metabolismo , Distribuição Tecidual
9.
Chem Biol Interact ; 294: 81-90, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30145136

RESUMO

Glutathione S-transferases (GSTs), the versatile phase II biotransformation enzymes, metabolize and detoxify a wide variety of toxic chemical compounds like carcinogens, chemotherapeutic drugs, environmental pollutants and oxidative stress products. GSTs are currently of great interest in drug discovery, nanotechnology and biotechnology because of their involvement in many major cellular processes. GSTs, which are either homo or hetero dimeric proteins mediate catalytic binding between glutathione (GSH) and an array of either endogenous or exogenous toxic compounds to form a highly soluble detoxified complex which is then eliminated. Polycyclic aromatic hydrocarbons (PAHs) which are composed of two or more benzene rings bonded as linear, cluster or angular arrangements are used as intermediaries in pharmaceuticals, agricultural products, photographic products, thermosetting plastics, lubricating materials and other chemical products. Foods those cooked at high temperatures by grilling, roasting, frying and smoking are the main sources for the persistent bio-accumulation of PAHs in food chain. The carcinogenic, mutagenic and immunosuppressive effects of PAHs are well established. A well-known polycyclic aromatic hydrocarbon, methylcholanthrene is a potential carcinogenic, neurotoxic, mutagenic and tumour causing agent that is used as an experimental carcinogen in biological research. Methylcholanthrene converts into reactive metabolites when it enters living cells and those reactive metabolites oxidize DNA, RNA, proteins and lipids and form DNA and protein adducts as well. GSTs play major role in the detoxification of reactive metabolites of methylcholanthrene by mediating catalytic binding with GSH to form a highly soluble detoxified complex which is then eliminated. This review summarizes the role of GSTs in the detoxification of a polycyclic aromatic hydrocarbon, methylcholanthrene.


Assuntos
Glutationa Transferase/metabolismo , Inativação Metabólica/efeitos dos fármacos , Metilcolantreno/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Humanos , Metilcolantreno/química , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
10.
Pathophysiology ; 25(4): 285-292, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29908890

RESUMO

Glutathione S-tranferases (GSTs) are phase II drug metabolizing enzymes, they play crucial role in detoxification of environmental pollutants, carcinogens, drugs, xenobiotics and oxidative stress products. Genetic differences in expression and activity of GSTs are due to the existence of polymorphic alleles which encode them. Because of genetic polymorphism the GST activity has altered that lead to the increased susceptibility for toxic chemical compounds. GST genetic polymorphism is the main reason for many neurological dysfunctions. GST has over expressed in epileptic brain and pi (π) GST has used to predict stroke; mu (µ) and pi (π) GST are over expressed in Alzheimer's disease (AD). Null and single nucleotide polymorphism of GST has associated with many neurodisorders. Over all, it can be concluded that the GST genetic polymorphism has associated with neurodegenerative diseases.

11.
J Food Drug Anal ; 26(1): 201-210, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29389556

RESUMO

The present study aimed to investigate the effects of the various parts of Ficus carica L. (figs) on antioxidant, antidiabetic, and antiobesogenic effects in vitro. Fruit, leaves, and stembark of the F. carica plant were sequentially extracted using organic and inorganic solvents and their total polyphenol and flavonoid contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes), and antiobesogenic (antilipase) activities were measured using several experimental models. The fruit ethanolic extract contained a high quantity of polyphenols and flavonoids (104.67±5.51 µg/mL and 81.67±4.00 µg/mL) compared with all other extracts. The activity of the ethanolic extract of F. carica fruit was significantly (p<0.05) higher than all other extracts and parts of the plant in terms of antioxidative, antidiabetic, and antiobesogenic effects. The IC50 values of the fruit ethanolic extract in terms of antioxidative (134.44±18.43 µg/mL), and inhibition of α-glucosidase (255.57±36.46 µg/mL), α-amylase (315.89±3.83 µg/mL), and pancreatic lipase (230.475±9.65 µg/mL) activity indicate that the activity of fruit ethanolic extract is better than all other extracts of the plant. The gas chromatography-mass spectroscopy analysis of the fruit ethanolic extract showed the presence of a number of bioactive compounds such as butyl butyrate, 5-hydroxymethyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, 9Z,12Z-octadecadienoic acid, stearic acid, sitosterol, 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, and 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one. The results of this study suggest that the ethanolic extract of the fruit of F. carica may have potential antidiabetic and antiobesogenic agents.


Assuntos
Inibidores Enzimáticos/farmacologia , Ficus/química , Síndrome Metabólica/enzimologia , Extratos Vegetais/farmacologia , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
12.
Cancer Biother Radiopharm ; 33(10): 427-437, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31287718

RESUMO

Background: Pterocarpus santalinus popularly known as Red Sanders is an endemic species confined to Southern part of Eastern Ghats of India especially in Andhra Pradesh and has high demand for its economical importance for its use in treatment of human ailments. Materials and Methods: In the present study, the authors have examined the presence of various phytochemicals in the chloroform extract of P. santalinus heartwood (PSCE, Pterocarpus santalinus chloroform extract) by qualitative and quantitative assays. PSCE was further used to evaluate its antioxidant and metal reducing capacity. Radioprotective property was also evaluated in various subcellular and cellular model systems. Results: The phytochemical screening study showed that the extract was positive for carbohydrates, cardiac glycosides, flavonoids, phenols, tannins, saponins, and terpenoids and was negative for alkaloids, steroids, and phlobatannins. Contents of total phenol, total flavonoids, total anthocyanin, and total tannin in the PSCE are 404 µg/mg in terms of gallic acid equivalents, 22.6 µg/mg in terms of quercetin equivalents, 0.066 mg in terms of cyanidin-3-glucoside (cyn-3-glu) equivalents, and 12.477 g/L, respectively. This extract exhibited significant radical scavenging activity against model free radical 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+), 1,1-diphenyl picrylhydrazyl, and biologically important nitric oxide. It has significant metal reducing capacity as monitored by ferric and molybdenum reduction assay. PSCE showed a concentration dependent radioprotection to plasmid pBR322 DNA and lipids of the mitochondrial membranes. Their study also showed that PSCE protected splenic lymphocytes against radiation induced cell death, DNA double strand breaks, and lipid peroxidation as monitored by propidium iodide staining, γ-H2AX assay, neutral comet assay, and TBARS assay, respectively. Addition of PSCE to lymphocytes scavenged radiation derived reactive oxygen species, restored loss of thiol content, and inhibited cellular apoptosis. Conclusions: PSCE possesses high antioxidant activity and exhibited very good radioprotective property in cell free and cellular model systems.


Assuntos
Antioxidantes/farmacologia , Linfócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pterocarpus , Protetores contra Radiação/farmacologia , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Clorofórmio/química , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Masculino , Camundongos Endogâmicos BALB C , Oxirredução , Compostos Fitoquímicos/química , Extratos Vegetais/química , Protetores contra Radiação/química , Baço , Raios Ultravioleta
13.
Interdiscip Toxicol ; 11(2): 115-121, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31719782

RESUMO

Glutathione S-transferases (GSTs) are major defence enzymes of the antioxidant enzymatic system. Cytosolic GSTs are more involved in the detoxification than mitochondrial and microsomal GSTs. GSTs are localized in the cerebellum and hippocampus of the rat brain. Acrylamide (AC) is a well assessed neurotoxin of both animals and humans and it produces skeletal muscle weakness and ataxia. AC is extensively used in several industries such as cosmetic, paper, textile, in ore processing, as soil conditioners, flocculants for waste water treatment and it is present in daily consumed food products, like potato chips, French fries, bread, breakfast cereals and beverages like coffee; it is detected on tobacco smoking. GST acts as a biomarker in response to acrylamide. AC can interact with DNA and therefore generate mutations. In rats, low level expression of glutathione S-trasferase (GST) decreases both memory and life span. The major aim of this review is to provide better information on the antioxidant role of GST against AC induced neurotoxicity and genotoxicity.

14.
Pharmacogn Mag ; 13(51): 385-392, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28839361

RESUMO

The prevalence of overweight-obesity and associated comorbidities have reached alarming levels necessitating the need to explore effective therapeutics. In the present work, we demonstrated the promising antiobesity activity of ethanolic fraction of Terminalia tomentosa bark (EFTT) in diet induced obese rat model. High Fat Diet (HFD)-fed obese rats were orally administered with EFTT (50, 100 and 200 mg/kg body weight). Changes in body weight, body composition, bone mineral concentration, bone mineral density, plasma glucose, insulin, leptin, adiponectin, circulatory and tissue lipid profiles, and the activities of liver antioxidant enzymes, key lipid metabolic enzymes and mRNA expressions of fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPAR-γ), leptin and tumor necrosis factor alpha (TNF-α) were assessed in experimental rats in the presence and absence of EFTT. At a dose of 200 mg/kg b.wt, EFTT has substantially attenuated body weight and related patho-physiological alterations in HFD-induced obese rats. These findings were correlated with histological observations of adipose tissue. The therapeutic activity of EFTT could be possibly through restoration of antioxidants status, regulation of key lipid metabolizing enzymes, expression of FAS, leptin, PPAR-γ and by synchronized control of energy metabolism in liver and adipose tissue.

15.
Mol Cell Biochem ; 432(1-2): 25-32, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28258439

RESUMO

Dietary measures and plant-based therapies as prescribed by native systems of medicine have gained attraction among diabetics with claims of efficacy. The present study investigated the effects of S-Allylcysteine (SAC) on body weight gain, glucose, insulin, insulin resistance, and nitric oxide synthase in plasma and argininosuccinate synthase (AS) and argininosuccinate lyase (ASL), lipid peroxides and antioxidant enzymes in aorta of control and streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Changes in body weight, glucose, insulin, insulin resistance, and antioxidant profiles of aorta and mRNA expressions of nitric oxide synthase, AS, and ASL were observed in experimental rats. SAC (150 mg/kg b.w) showed its therapeutic effects similar to gliclazide in decreasing glucose, insulin resistance, lipid peroxidation, and increasing body weight; insulin, antioxidant enzymes, and mRNA levels of nitric oxide synthase, argininosuccinate synthase, and argininosuccinate lyase genes in STZ-NA rats. Histopathologic studies also revealed the protective nature of SAC on aorta. In conclusion, garlic and its constituents mediate the anti-diabetic potential through mitigating hyperglycemic status, changing insulin resistance by alleviating endothelial dysregulation in both plasma and tissues.


Assuntos
Aorta/metabolismo , Cisteína/análogos & derivados , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/metabolismo , Animais , Aorta/patologia , Cisteína/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Endotélio Vascular/patologia , Masculino , Ratos , Ratos Wistar
16.
Can J Diabetes ; 40(5): 442-448, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27373435

RESUMO

OBJECTIVES: We evaluated the effects of S-allylcysteine (SAC) on biomarkers of the polyol pathway in streptozotocin-nicotinamide (STZ-NA)-induced diabetes in rats. METHODS: Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (55 mg kg-1 bw-1) and NA (110 mg kg-1 bw-1). SAC (150 mg kg-1 bw-1) was orally administered to the rats with diabetes for 45 days to assess its effects on blood glucose, insulin, insulin resistance, glycated hemoglobin, aldose reductase (AR), sorbitol dehydrogenase (SDH), sorbitol, fructose, thiobarbituric acid-reactive substances (TBARS), hydroperoxide, hemoglobin and glutathione (GSH). RESULTS: On SAC administration in the rats with diabetes, the levels of blood glucose, insulin resistance, glycated hemoglobin, AR, SDH, sorbitol, fructose, TBARS and hydroperoxide increased significantly (p<0.05), whereas those of insulin, hemoglobin and GSH decreased. SAC showed therapeutic effects similar to those of gliclazide in decreasing blood glucose, AR, SDH, sorbitol, fructose, glycosylated hemoglobin, TBARS and hydroperoxides levels and significant increases in insulin, hemoglobin and GSH activity in rats with diabetes. Moreover, histopathologic studies also revealed the protective effect of SAC on pancreatic beta cells. CONCLUSIONS: The results indicate that SAC prevents complications of diabetes by reducing the influx of glucose in the polyol pathway, thereby elevating the GSH level and reducing the activities of AR and SDH. Therefore, SAC may have imperative implications for the deterrence and early treatment of type 2 diabetes.


Assuntos
Cisteína/análogos & derivados , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Polímeros/metabolismo , Aldeído Redutase/sangue , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Cisteína/farmacologia , Cisteína/uso terapêutico , Frutose/sangue , Glutationa/sangue , Hemoglobinas Glicadas/metabolismo , Hemoglobinas/metabolismo , Peróxido de Hidrogênio/sangue , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , L-Iditol 2-Desidrogenase/sangue , Ratos Wistar , Sorbitol/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
17.
Biometals ; 29(2): 187-210, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26796895

RESUMO

Aluminum (Al) stress is one of the serious limiting factors in plant productivity in acidic soils, which constitute about 50 % of the world's potentially arable lands and causes anywhere between 25 and 80 % of yield losses depending upon the species. The mechanism of Al toxicity and tolerance has been examined in plants, which is vital for crop improvement and enhanced food production in the future. Two mechanisms that facilitate Al tolerance in plants are Al exclusion from the roots and the ability to tolerate Al in the symplast or both. Although efforts have been made to unravel Al-resistant factors, many aspects remain unclear. Certain gene families such as MATE, ALMT, ASR, and ABC transporters have been implicated in some plants for resistance to Al which would enhance the opportunities for creating crop plants suitable to grow in acidic soils. Though QTLs have been identified related to Al-tolerance, no crop plant that is tolerant to Al has been evolved so far using breeding or molecular approaches. The remarkable changes that plants experience at the physiological, biochemical and molecular level under Al stress, the vast array of genes involved in Al toxicity-tolerance, the underlying signaling events and the holistic image of the molecular regulation, and the possibility of creating transgenics for Al tolerance are discussed in this review.


Assuntos
Alumínio/farmacologia , Produtos Agrícolas/crescimento & desenvolvimento , Poluentes do Solo/farmacologia , Solo/química , Adaptação Fisiológica , Produtos Agrícolas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genes de Plantas , Humanos , Concentração de Íons de Hidrogênio , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapas de Interação de Proteínas
18.
Mol Cell Endocrinol ; 419: 139-47, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26493465

RESUMO

Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism.


Assuntos
Biomarcadores/metabolismo , Catecóis/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Álcoois Graxos/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Benzazepinas/administração & dosagem , Benzazepinas/farmacologia , Peso Corporal/efeitos dos fármacos , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Resistência à Insulina , Interleucina-6/metabolismo , Masculino , Obesidade/induzido quimicamente , Obesidade/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
19.
Asian Pac J Trop Med ; 5(5): 391-5, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22546657

RESUMO

OBJECTIVE: To evaluate the insecticidal, antimicrobial and antioxidant activities of bulb extracts of Allium sativum (A. sativum). METHODS: Dried bulbs of A. sativum were extracted with different solvents and evaluated for insecticidal, antimicrobial and antioxidant activities. METHODS: Aqueous and methanol extracts showed highest insecticidal activity (mortality rate of 81% and 64% respectively) against the larvae of Spodoptera litura (S. litura) at a concentration of 1 000 ppm. With regard to antimicrobial activity, aqueous extract exhibited antibacterial activity against gram positive (Bacillus subtilis, Staphylococcus aureu,) and gram negative (Escherichia coli and Klebsiella pneumonia) strains and antifungal activity against Candida albicans. While methanol extract showed antimicrobial activity against all the tested micro organisms except two (Staphylococcus aureus and Candida albicans), the extracts of hexane, chloroform and ethyl acetate did not show any anti microbial activity. Minimum inhibitory concentration of aqueous and methanol extracts against tested bacterial and fungal strains was 100-150 µg/mL. Antioxidant activity of the bulb extracts was evaluated in terms of inhibition of free radicals by 2, 2'-diphenly-1-picrylhydrazyl. Aqueous and methanol extracts exhibited strong antioxidant activity (80%-90% of the standard). CONCLUSIONS: Antioxidant and antimicrobial activity of A. sativum against the tested organisms therefore, provides scientific basis for its utilization in traditional and folk medicine. Also, our results demonstrated the insecticidal efficacy of A. sativum against S. litura, a polyphagous insect.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Alho , Inseticidas/farmacologia , Extratos Vegetais/farmacologia , Animais , Candida albicans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Raízes de Plantas , Spodoptera/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
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